Treating COVID-19 in PD and other MD: A review of drug interactions
Mónica M. Kurtis, MD Hospital Ruber Internacional Madrid, Spain
August 26, 2020 Disclosures Mónica M. Kurtis has received honoraria for sponsored talks and consulting from Bial and Zambon, and travel expenses to attend scientific meetings by Boston Scientific. She has also received grants from the Madrid Neurology Association and is currently participating in a Michael J Fox Grant. PD and other movement disorders: Risk of COVID-19
• No data of increased risk per se • Increased risk of severity if infected • Male • Elderly • Nursing homes • Decreased lung capacity • Cognitive impairment: increased risk of confusion/delirium • Comorbidities: diabetes, cardiovascular disease (hypertension), obesity etc. covid-trials.org August 24-8-2020 Anti COVID-19 experimental drugs Antivirals
1. Remdesivir: vs SARS-CoV-2 (FDA approved) 3. Favipinavir: vs influenza (Asia)
• Broad spectrum antiviral nucleotide analogue • Broad spectrum antiviral
2. Lopinavir/ritonavir: vs HIV • RNA polymerase inhibitor
• RNA Protease inhibitor 4. Atazanavir: vs HIV
• Can prolong QTc interval 5. Ribavirin: vs Hepatitis C
• inhibits hepatic and intestinal CYP3A4 6. Ivermectin
• inhibits hepatic CYP2D6 Anti COVID-19 experimental drugs Antivirals
1. Remdesivir (RDV): vs SARS-CoV-2 (FDA approved) 3. Favipinavir: vs influenza (Asia)
• Broad spectrum antiviral nucleotide analogue • Broad spectrum antiviral
2. Lopinavir/ritonavir (LPV/R): vs HIV • RNA polymerase inhibitor
• RNA Protease inhibitor 4. Atazanavir: vs HIV
• Can prolong QTc interval 5. Ribavirin: vs Hepatitis C
• inhibits hepatic and intestinal CYP3A4 6. Ivermectin
• inhibits hepatic CYP2D6 Anti COVID-19 experimental drugs Inmunomodulators 1. Chloroquine: 1. Dexamathasone (DEX)
• QTc interval prolongation • increases hepatic/intestinal CYP3A4
• retinal toxicity, 2. Tocilizumab (TCZ): IL-6 receptor inhibitor + Many others: • inh hepatic CYP2D6 • vs rheumatic diseases. Colchicine 2. Hydroxychloroquine: • Can cause pancitopenia
• QTc interval prolongation Famotidine • Elevates liver enzymes and lipids
• (retinal toxicity) Daclafasvir 3. Sarilumab: IL-6 pathway
± Macrolid antibiotics 4. Siltuximab IL-6 pathway
• Azitromycine: QTc prolongation, ear toxicity 5. Anakinra: IL-1 pathway
• Claritromycine: QTc prolongation, ear toxicity 6. Interferon-beta
7. Convalescent plasma Webinar Outline
• Covid-19 drug interactions with MD drugs • Covid-19 drug interactions with other common drugs in MD patients Image by succo from Pixabay • Clinical cases COVID-19 drugs and MD medications: possible interactions PD Drugs
DEX RDV LPV/r TCZ
Levodopa L-dopa/BSZ OK OK OK
L-dopa/CD OK OK OK
Agonists Pramipexole OK OK OK OK Legend
Ropinirole OK OK OK OK prolongs QT or PR intervals Rotigotine OK OK OK OK Blue arrows: effect on COVID drugs Apomorphine OK OK OK
MAOB-I Selegiline OK OK OK OK • potentiates effect
Rasagiline OK OK OK OK • decreases effect
Safinamide OK OK OK OK Orange arrows: effect on MD drugs COMP-I Entacapone OK OK OK OK • potentiates effect Opicapone OK OK OK OK • decreases effect Others Amantadine OK OK OK PD Drugs
DEX RDV LPV/r TCZ
Levodopa L-dopa/BSZ OK OK OK
L-dopa/CD OK OK OK
Agonists Pramipexole OK OK OK OK Legend
Ropinirole OK OK OK OK prolongs QT or PR intervals Rotigotine OK OK OK OK Blue arrows: effect on COVID drugs Apomorphine OK OK OK
MAOB-I Selegiline OK OK OK OK • potentiates effect
Rasagiline OK OK OK OK • decreases effect
Safinamide OK OK OK OK Orange arrows: effect on MD drugs COMP-I Entacapone OK OK OK OK • potentiates effect Opicapone OK OK OK OK • decreases effect Others Amantadine OK OK OK PD Drugs
DEX RDV LPV/r TCZ
Levodopa L-dopa/BSZ OK OK OK
L-dopa/CD OK OK OK
Agonists Pramipexole OK OK OK OK Legend
Ropinirole OK OK OK OK prolongs QT or PR intervals Rotigotine OK OK OK OK Blue arrows: effect on COVID drugs Apomorphine OK OK OK
MAOB-I Selegiline OK OK OK OK • potentiates effect
Rasagiline OK OK OK OK • decreases effect
Safinamide OK OK OK OK Orange arrows: effect on MD drugs COMP-I Entacapone OK OK OK OK • potentiates effect Opicapone OK OK OK OK • decreases effect Others Amantadine OK OK OK Tremor drugs
DEX RDV LPV/r TCZ
Gabapentine OK OK OK OK
Pregabaline OK OK OK OK Legend
OK OK OK OK Levetiracetam prolongs QT or PR intervals
Clonazepam OK OK OK Blue arrows: effect on COVID drugs
• potentiates effect Zonisamide OK OK
• decreases effect Topiramate OK OK Orange arrows: effect on MD drugs Propranolol OK OK OK • potentiates effect Primidone OK OK • decreases effect Dystonia drugs
DEX RDV LPV/r TCZ
Trihexyphenidyl OK OK OK OK
Legend Pregabaline OK OK OK OK prolongs QT or PR intervals
Gapapentine OK OK OK OK Blue arrows: effect on COVID drugs
• potentiates effect Clonazepam OK OK OK • decreases effect
Botulinum toxin OK OK OK OK Orange arrows: effect on MD drugs
• potentiates effect Tetrabenazine OK OK OK • decreases effect Chorea and tic drugs
DEX RDV LPV/r TCZ
Guanfacine OK OK OK
Clonazepam OK OK OK
Botulinum toxin OK OK OK OK Legend
OK OK Aripriprazole prolongs QT or PR intervals
Pimozide OK OK Blue arrows: effect on COVID drugs
Risperidone OK OK OK • potentiates effect Haloperidol OK OK OK • decreases effect OK Olanzapine OK OK OK Orange arrows: effect on MD drugs TBZ OK OK OK • potentiates effect Clozapine OK OK • decreases effect COVID-19 drugs and other frequently used medications in MD patients: possible interactions Depression – Anxiety drugs
DEX RDV LPV/r TCZ
Duloxetine OK OK OK OK
Venlafaxine OK OK OK OK Legend Desvenlafaxine OK OK OK prolongs QT or PR intervals Fluoxetine OK OK OK OK Blue arrows: effect on COVID drugs Buproprion OK OK OK • potentiates effect Sertraline OK OK OK • decreases effect Citalopram OK OK OK Orange arrows: effect on OTHER drugs Escitalopram OK OK OK • potentiates effect Paroxetine OK OK OK • decreases effect Amitryptiline OK OK Insomnia or Anxiety drugs
DEX RDV LPV/r TCZ
Lorazepam OK OK OK OK
Lormetazepam OK OK OK OK Legend Clonazepam OK OK OK prolongs QT or PR intervals Bromazepam OK OK OK Blue arrows: effect on COVID drugs Alprazolam OK OK • potentiates effect Diazepam OK OK OK • decreases effect Zopiclone OK Ok OK Orange arrows: effect on OTHER drugs Zolpidem OK OK • potentiates effect Trazodone OK OK • decreases effect Mirtazapine OK OK OK Dementia drugs
DEX RDV LPV/r TCZ
Legend Rivastigmine OK OK OK OK prolongs QT or PR intervals
Blue arrows: effect on COVID drugs Donepezil OK OK • potentiates effect
• decreases effect Galantamine OK OK Orange arrows: effect on OTHER drugs
• potentiates effect Memantine OK OK OK OK • decreases effect Confusion/Agitation drugs
DEX RDV LPV/r TCZ
Quetiapine OK OK
Clozapine OK OK Legend
OK OK OK OK Amisulpiride prolongs QT or PR intervals
Aripiprazole OK OK Blue arrows: effect on COVID drugs
• potentiates effect Palinperidone OK OK OK
• decreases effect Haloperidol OK OK OK Orange arrows: effect on OTHER drugs Risperidone OK OK OK • potentiates effect Olanzapine OK OK OK OK • decreases effect Nausea and gastroenteritis
DEX RDV LPV/r TCZ
Domperidone OK OK Legend
prolongs QT or PR intervals
OK OK OK OK Metoclopramide Blue arrows: effect on COVID drugs
• potentiates effect Ondansetron OK OK • decreases effect
Orange arrows: effect on OTHER drugs
• potentiates effect Loperamide OK OK OK • decreases effect Gastric protectors
DEX RDV LPV/r TCZ Legend
prolongs QT or PR intervals Esomeprazol OK OK OK
Blue arrows: effect on COVID drugs Pantoprazol OK OK OK • potentiates effect
OK OK Lansoprazol • decreases effect
Omeprazol OK OK OK Orange arrows: effect on OTHER drugs
• potentiates effect Famotidine OK OK OK OK • decreases effect Antiaggregation/ Anticoagulation
DEX RDV LPV/r TCZ
Aspirin GI tox OK OK OK
Clopidogrel OK OK
Legend Enoxaparine OK OK OK
Heparine OK OK OK prolongs QT or PR intervals
Acenocumarol OK OK Blue arrows: effect on COVID drugs
Warfarin OK OK • potentiates effect
• decreases effect Dabigatran OK OK OK
Edoxaban OK OK OK Orange arrows: effect on OTHER drugs
Rivaroxaban OK OK • potentiates effect
Apixaban OK OK • decreases effect Clinical cases Case 1. Phillip: 55 y/o with flu like symptoms PD since 2017. Insomnia
• Treatment:
• Pramipexole 3mg ER 1-0-0 + Rasagiline 1mg 1-0-0 + Amantadine 100mg 1-1-0
• Zolpidem 10mg 0-0-1
• 10 day history of flu like syndrome, dry cough
• Exam: O2 97%; BP =150/80; HR 84 bpm
• Blood work: Leukocytes: 6.50x103, Lymphocyte count: 1.400; Ferritin 450 (30-400); D-dimers: 500µg/l (68-494), CRP: 3.2 (0-0.5)
• X-ray: ground glass opacification of the LIL
• PCR : positive for SARS-CoV-2 PD patient with mild – moderate COVID-19 Outpatient treatment: Paracetamol/cough medicine
• Pramipexole 3mg ER 1-0-0 • Amantadine 100mg 1-1-0
• Rasagiline 1mg 1-0-0 • Zolpidem 10mg 0-0-1
1. No changes in PD meds 2. Other drugs
• No change
• Need for thromboprophylaxis? MD patient with mild COVID-19 Outpatient treatment 80% of patients (1) 1. Symptomatic treatment
• paracetamol, acetaminophen - preferred over NSAI
• Cough medication?: dextrometorphan or benzonatate
2. NO changes in MD treatment or OTHER treatments
3. Avoid nebulizations NO SPECIFIC DRUGS 4. Sleep in prone position
5. Evaluate need for thromboprophylaxis outside clinical trials
6. Evaluate need for home oxygen therapy 1. World Health Organization. Report of the WHO- China joint mission on coronavirus disease 2019 7. Strict measures for respiratory and contact ISOLATION (COVID-19), 2020. https://www.who.int/publications- detail/report-of-the-who-china-joint-mission-on- 8. Close telemedicine monitoring coronavirus-disease-2019-(covid-19) Case 2. Edward: 75 y/o man with dyspnea PD since 2016. MCI. Atrial Fib. HTension. HLipidemia • Treatment
• Sinemet Plus 1-1-1-1 • Atorvastatine 20 0-0-1
• Rivastigmine 9.5 mg sc • Candesartan 16 1-0-1
• Quetiapine 25 mg 0-0-1/2 • Rivaroxaban 15mg 1-0-0
• 3 day history of diarrhea, low fever <38º, headache, dry cough, dyspnea, confusion
• Exam: O2 89%; BP 125/70; HR 60 bpm arrythmic, T 35.6 C X-ray: bilateral ground glass • Blood work: Leukocytes: 4.30x103, Lymphocyte count: 800; Ferritin opacification 1445; D-dimers: 1100 µg/l, CRP: 12.0
• PCR : positive for SARS-CoV-2 PD with moderate-severe COVID-19: hospitalization Dexamethasone? + Remdesivir? If not available: TCZ? LPV/r?
• Sinemet Plus 1-1-1-1 • Atorvastatine 20 0-0-1 • Rivastigmine 9.5 mg sc • Candesartan 16 1-0-1 • Quetiapine 25 mg 0-0-1/2 • Rivaroxaban 15mg 1-0-0
1. No changes in PD meds, except: 2. Other drugs: • If not tolerating by mouth: SUBSTITUTE with • Rivastigmine: no change rotigotine patch (4mg = 100 mg LED) • Quetiapine: • IF TCZ: decrease dose due to interactions with • IF DEX: may need to increase dose L-dopa • IF LPV/r: STOP quetiapine • BP meds and statin: no change • Anti-coagulant: change to low wt heparin • Add gastric protector Case 3. Maria 70 y/o with acute weakness ET since youth. Diabetes.
• Treatment:
Primidone 4mg 1-1-0
Metformin 1-0-1
• 3 day history of progressive leg weakness.
• Exam: O2 92%; BP =150/70; HR 86 bpm. Weakness in LL with areflexia.
• Blood work: Leukocytes: 4.00x103, Lymphocytes: 800; Ferritin 1550; D-dimers: 240 µg/l, CRP: 10.5 (0-0.5).
• X-ray: normal
• CSF: proteins 103 mg/dL; glucose 90, cell count 0
• PCR : positive for SARS-CoV-2 ET patient COVID-19: Hospitalization Dexamethasone? + Remdesivir? or Tocilizumab? LPV/r?
• Primidone 4mg 1-1-0 • Metformin 1-0-1
1. No changes in ET meds, except: 2. Other drugs:
• If DEX or LPV/R • Monitor sugar levels
• STOP Primidone since decreases effect • DEX decreases effect of Metformin of anti COVID-19 drugs • Add gastric protector
• Add anticoagulation
• Add inmunogammaglobuline iv? Susana. 45 y/o with rash Tourette Syndrome since childhood. Anxiety.
• Treatment:
• Pimozide 4mg 1-1-0 • Trazodone 100mg 0-0-1
• Clonacepam 0.5 mg 1-1-1 • Botulinum toxin for cervical tics
• 5 day history of headache and anosmia. Rash for 2 days.
• Exam: O2 94%; BP =140/80; HR 76 bpm. Eccema.
• Blood work: Leukocytes: 4.50x103, Lymphocytes: 600; Ferritin 1250; D-dimers: 340 µg/l, CRP: 6.5 (0- 0.5).
• X-ray: normal
• PCR : positive for SARS-CoV-2 Tourette patient COVID-19: Hospitalization Dexamethasone? + Remdesivir? Tocilizumab?
• Pimozide 4mg 1-1-0 • Trazodone 100mg 0-0-1
• Clonacepam 0.5 mg 1-1-1 • Botulinum toxin for cervical tics
1. No changes in Tourette meds, except:
• If DEX 2. Other drugs:
• Interaction with Pimozide: increased tics • Add gastric protector
• Interaction with Trazodone • Add anticoagulation
• If LPV/r • Add antihistamine for rash?
• Monitor clonacepam effects Conclusions
1. Always consider the possibility of drug interactions between COVID-19 treatments and MD treatments
2. MD patients should continue taking their medications during infection whenever possible. Beware of stopping meds abruptly (i.e. neuroleptic maligant syndrome)
3. Assess the possibility of drug interactions between COVID-19 treatments and other drugs that MD patients are taking or are going to need while being treated for COVID-19.
4. Treat confusion. Remember patients are isolated.
5. Check for interactions before prescribing because consequences can be lethal (check references) References
• https://www.covid19-druginteractions.org/ • https://reference.medscape.com/drug-interactionchecker • https://www.drugs.com/drug_interactions.html • https://www.drugbank.ca/drugs • https://www.uptodate.com/contents/search Acknowlegements
Dr. Pablo Mir
Dr. Daniel Macias
Dr. Celia Delgado
Movement Disorders Group of the Spanish National Neurology Society
THANK-YOU for your attention